Clinical Trial: Immunosuppression With Mycophenolate Mofetil and Cyclosporine in Preventing Graft-Versus-Host Disease in Patients Undergoing Donor Peripheral Stem Cell Transplantation for Hematologic Malignancies or Metastatic Renal Cell Carcinoma

This study has been suspended.

Sponsors and Collaborators: Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Giving different schedules of mycophenolate mofetil and cyclosporine may be effective in reducing graft-versus-host disease in patients undergoing donor peripheral stem cell transplantation for hematologic malignancies (cancer) and metastatic renal cell carcinoma.

PURPOSE: Phase I/II trial to study the effectiveness of immunosuppression using a lengthened schedule of mycophenolate mofetil and a shortened schedule of cyclosporine in reducing graft-versus-host disease in patients who are undergoing donor peripheral stem cell transplantation for hematologic cancer or metastatic renal cell carcinoma.

Condition Treatment or Intervention Phase
childhood Hodgkin's lymphoma
childhood non-Hodgkin's lymphoma
Graft Versus Host Disease
hematopoietic and lymphoid cancer
kidney and urinary cancer
 Drug: cyclosporine
 Drug: fludarabine
 Drug: mycophenolate mofetil
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: chemotherapy
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: graft versus tumor induction
 Procedure: peripheral blood stem cell transplantation
 Procedure: radiation therapy
 Procedure: supportive care/therapy
Phase I
Phase II

MedlinePlus related topics:  Hodgkin's Disease;   Immune System and Disorders;   Lymphoma

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I/II Study of Prolonged Mycophenolate Mofetil and Truncated Cyclosporine Postgrafting Immunosuppression to Reduce Life-Threatening Graft-Versus-Host Disease After Unrelated Donor Peripheral Blood Stem Cell Transplantation Using Nonmyeloablative Conditioning in Patients With Hematologic Malignancies or Metastatic Renal Cell Carcinoma

Further Study Details: 

OBJECTIVES: Primary

Secondary

  • Compare the incidence of acute and chronic GVHD in patients treated with this regimen vs patients treated on protocols and .
  • Compare the utilization of corticosteroids in patients treated with this regimen vs patients treated on protocols and .
  • Compare the survival of patients treated with this regimen vs patients treated on protocols and .

OUTLINE: This is a multicenter study.

  • Conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -4 to -2 and low-dose total body irradiation (TBI) on day 0.
  • Allogeneic hematopoietic stem cell transplantation (HSCT): After the completion of TBI, patients undergo allogeneic HSCT on day 0.
  • Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 80 in the absence of acute graft-versus-host disease (GVHD). Patients also receive oral mycophenolate mofetil (MMF) 3 times daily on days 0-29 and then, in the absence of GVHD, twice daily on days 30-149. MMF is tapered beginning on day 150 and continuing until day 180. Patients are followed at 6 months, 12 months, 18 months, and 24 months and then annually for 5 years after HSCT.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 1.5 years.

Eligibility

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of either of the following:
  • Hematologic malignancy
  • Meeting 1 of the following criteria:
  • Over 50 years of age with a hematologic malignancy treatable by unrelated hematopoietic stem cell transplantation (HSCT)
  • 50 years of age and under with a hematologic malignancy treatable by allogeneic HSCT and considered to be at high risk for regimen-related toxicity associated with a conventional transplantation (greater than 40% risk of transplant-related mortality) due to a preexisting medical condition or prior therapy OR refused a conventional HSCT
  • Including, but not limited to the following:
  • Intermediate- or high-grade non-Hodgkin's lymphoma (NHL)
  • Not eligible for autologous HSCT or failed autologous HSCT
  • Low-grade NHL
  • Less than 6 months duration of complete remission (CR) between courses of conventional therapy
  • Chronic lymphocytic leukemia
  • Refractory to fludarabine
  • Hodgkin's lymphoma
  • Failed prior front-line therapy
  • Multiple myeloma
  • Received prior chemotherapy (consolidation of chemotherapy by autografting prior to nonmyeloablative HSCT is allowed)
  • Acute myeloid leukemia (AML)
  • Less than 5% marrow blasts at the time of transplantation
  • Acute lymphoblastic leukemia
  • Less than 5% marrow blasts at the time of transplantation
  • Chronic myelogenous leukemia (CML)
  • Chronic phase or accelerated phase
  • Prior autografts after high-dose therapy OR prior intensive chemotherapy with filgrastim (G-CSF)-mobilized peripheral blood mononuclear cell autologous or conventional HSCT for advanced CML allowed provided disease is in CR or chronic phase and there are less than 5% marrow blasts at the time of transplantation
  • Myelodysplastic syndromes (MDS) or myeloproliferative disorder
  • Refractory anemia (RA)
  • RA with ringed sideroblasts
  • Patients with greater than 5% marrow blasts (including those with transformation to AML) must receive cytotoxic chemotherapy and achieve less than 5% marrow blasts at the time of transplantation
  • Metastatic renal cell carcinoma (RCC) not amenable to surgical cure OR history of or active histologically or radiologically confirmed metastatic disease, including 1 of the following histological types:
  • Clear cell
  • Papillary
  • Medullary
  • No rapidly progressive intermediate- or high-grade NHL
  • No history of brain metastases (RCC patients)
  • No CNS involvement with disease refractory to intrathecal chemotherapy
  • No other non-hematological tumors except RCC
  • Available unrelated donor
  • Matched for HLA-A, B, C, DRB1, and DQB1
  • Only a single allele disparity is allowed for HLA-A, B, or C
  • No positive anti-donor cytotoxic crossmatch
  • No patient and donor pairs homozygous at a mismatched allele in the graft rejection vector
  • No marrow donors NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age

  • See Disease Characteristics
  • Any age

Performance status

  • Karnofsky 60-100% (70-100% for RCC patients)

Life expectancy

  • At least 6 months (RCC patients)

Hematopoietic

  • Not specified

Hepatic

Renal

  • Not specified

Cardiovascular

  • Cardiac ejection fraction at least 35%*
  • No hypertension greater than grade II NOTE: *Ejection fraction required for patients with a history of anthracycline exposure or cardiac disease

Pulmonary

  • DLCO at least 40%
  • No requirement for continuous supplementary oxygen
  • Pulmonary nodules allowed provided study enrollment is approved by the principal investigator

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 1 year after study participation
  • HIV negative
  • No fungal infection with radiological progression after prior amphotericin B or active triazole therapy for more than 1 month
  • No vertebral instability (RCC patients)

PRIOR CONCURRENT THERAPY: Biologic therapy

  • See Disease Characteristics
  • Prior cytokine therapy allowed
  • Prior rituximab allowed
  • No concurrent growth factors for 1 month after HSCT

Chemotherapy

  • See Disease Characteristics
  • More than 2 weeks since prior intensive chemotherapy, excluding low-dose cytarabine and chlorambucil

Endocrine therapy

  • Not specified

Radiotherapy

Surgery

  • Not specified

Other

  • More than 2 weeks since prior cytotoxic agents for cytoreduction, excluding hydroxyurea and imatinib mesylate

Location Information


California
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States

Colorado
      Rocky Mountain Cancer Centers - Denver Midtown, Denver,  Colorado,  80218,  United States

Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States

Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States

Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112,  United States

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States

Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States

Denmark
      Rigshospitalet, Copenhagen,  2100,  Denmark

Germany
      Medizinische Universitaetsklinik I, Cologne,  D-50924,  Germany

      Universitaet Leipzig, Leipzig,  D-04103,  Germany

      Universitaetsklinikum Tuebingen, Tuebingen,  D-72076,  Germany

Italy
      Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino, Turin,  10126,  Italy

Study chairs or principal investigators

Michael B. Maris, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000346473; FHCRC-1668.00; NCT00078858
Record last reviewed:  February 2005
Last Updated:  February 9, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00078858
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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